The role of adjuvants in overcoming antibacterial resistance due to enzymatic drug modification
Christy El-Khoury, Elissar Mansour, Yori Yuliandra, Felcia Lai, Bryson A. Hawkins, Jonathan J. Du, Eric J. Sundberg, Nicolas Sluis‐Cremer, David E. Hibbs, Paul W. Groundwater
Abstract
Antibacterial resistance is a prominent issue with monotherapy often leading to treatment failure in serious infections. Many mechanisms can lead to antibacterial resistance including deactivation of antibacterial agents by bacterial enzymes. Enzymatic drug modification confers resistance to β-lactams, aminoglycosides, chloramphenicol, macrolides, isoniazid, rifamycins, fosfomycin and lincosamides. Novel enzyme inhibitor adjuvants have been developed in an attempt to overcome resistance to these agents, only a few of which have so far reached the market. This review discusses the different enzymatic processes that lead to deactivation of antibacterial agents and provides an update on the current and potential enzyme inhibitors that may restore bacterial susceptibility.